title: The miR-310/13 cluster antagonizes β-catenin function in the regulation of germ and somatic cell differentiation in the Drosophila testis.
abstract: MicroRNAs (miRNAs) are regulators of global gene expression and function in a broad range of biological processes. Recent studies have suggested that miRNAs can function as tumor suppressors or oncogenes by modulating the activities of evolutionarily conserved signaling pathways that are commonly dysregulated in cancer. We report the identification of the miR-310 to miR-313 (miR-310/13) cluster as a novel antagonist of Wingless (Drosophila Wnt) pathway activity in a functional screen for Drosophila miRNAs. We demonstrate that miR-310/13 can modulate Armadillo (Arm; Drosophila β-catenin) expression and activity by directly targeting the 3'-UTRs of arm and pangolin (Drosophila TCF) in vivo. Notably, the miR-310/13-deficient flies exhibit abnormal germ and somatic cell differentiation in the male gonad, which can be rescued by reducing Arm protein levels or activity. Our results implicate a previously unrecognized function for miR-310/13 in dampening the activity of Arm in early somatic and germline progenitor cells, whereby inappropriate/sustained activation of Arm-mediated signaling or cell adhesion may impact normal differentiation in the Drosophila male gonad.
authors.affiliation: Department of Pharmacology and the NYU Cancer Institute, New York University Langone Medical Center, 522 First Avenue, SRB #1211, New York, NY 10016, USA.
authors.forename: Raluca
authors.initials: R
authors.lastname: Pancratov
authors.forename: Felix
authors.initials: F
authors.lastname: Peng
authors.forename: Peter
authors.initials: P
authors.lastname: Smibert
authors.forename: Shiuan
authors.initials: S
authors.lastname: Yang
authors.forename: Emily Ruth
authors.initials: ER
authors.lastname: Olson
authors.forename: Ciaran
authors.initials: C
authors.lastname: Guha-Gilford
authors.forename: Amol J
authors.initials: AJ
authors.lastname: Kapoor
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Liang
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
authors.forename: Maria Sol
authors.initials: MS
authors.lastname: Flaherty
authors.forename: Ramanuj
authors.initials: R
authors.lastname: DasgGupta
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005854:Germ Cells / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D013737:Testis / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; C000603450:MIRN310 microRNA, Drosophila; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C115159:pan protein, Drosophila
keywords: Armadillo; Beta-catenin; MicroRNA; Stem cells; Wingless